tbuckley/cabot-search huggingface dataset:
PB1795: BIO-INSPIRED NANOMEDICINE FOR TARGETED ACUTE MYELOID LEUKEMIA IMMUNOTHERAPY
Authors: X. Wang, R. Huang, K. Fang, X. Zhang
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy linked to molecular alterations and disease remission requires multiple chemotherapies. In spite of the recent approval of new promising targeted therapies, the clinical outcome of AML patients remains suboptimal with high relapse rate, prompting the search for synergistic therapeutic approaches. In recent years, the rise of nanotechnology provides new horizons in AML treatment by using versatile and safe nano systems. Aims: To achieve the targeted AML treatment by virtue of MnO2 nanostructure-based immune- and chemotherapy synergy. Methods: A bio-inspired nanomedicine (LHMD) nanomedicine was first designed by coating AML cell membrane onto DOX-loaded hollow MnO2 nano-carrier. The nanostructure of LHMD was observed and characterized. The cell viability, cell injury behavior, homologous targeting effect and immune activation after LHMD nanomedicine treatment were investigated in vitro. In vivo BM homing properties and anti-AML efficacy were also analyzed in the AML mice model. Results: We developed LHMD to specifically target in the BM and deliver chemotherapeutic agents, DOX, for potent immune therapy and chemotherapy against AML. After cell internalization of nanomedicine, LHMD was disassembled owing to the high level of GSH and endosomal acid in tumor cells, which mediated the release of DOX and Mn2+. DOX destroyed dsDNA breakage to further induce cellular immunogenic death (ICD), thus killing leukemia cells. Mn2+ triggered the STING pathway activation in macrophage and sensitize the cGAS to recognize of dsDNA, thus further boosting innate immunity. Summary/Conclusion: A bio-inspired nanomedicine was constructed by integrating Mn2+ mediated STING pathway activation for synergized acute myeloid leukemia chemo- and immunotherapy.
PB1925: VENETOCLAX IN COMBINATION WITH AZACITIDINE OR LOW-DOSE CYTARABINE IN PATIENTS WITH HIGH-RISK MDS AND AML - EXPERIENCE OF A CZECH HAEMATOLOGY CENTRE.
Authors: L. Minarik, T. Stopka, Z. Zemanova, A. Jonasova
Journal: HemaSphere (2022)

Background: The prognosis of older patients diagnosed with high-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML) ineligible of intensive treatment that are progressing on hypomethylating therapy (HMA) remains dismal. Recently two international, randomized, placebo-controlled clinical trials VIALE-A and VIALE-C compared administration of azacitidine (AZA) or low-dose cytarabine (LD-AraC) alone or in combination with BCL-2 inhibitor venetoclax (VTX) in patients diagnosed with de novo AML. Results were promising with significant prolongation of median overall survival (OS) and achieving early remissions in combination cohort groups. Recently was published also trials involving 78 HMA-naïve high-risk MDS patients (Garcia JS et al., 2020) and a similar trial of 44 patients (Zeidan AM et al. 2020). Aims: To monitor the toxicity of therapy, to identify how many patients received reduced treatment due to cytopenia and to identify markers associated with worse outcome in patients treated with VTX combination therapy. Methods: Panel of 33 genes frequently mutated in MDS was used for mutation screening. Description of Cohort: Patients were treated either with combination of AZA-VTX or LD-AraC-VTX. Our cohort consists of 22 patients (males, N=12, females, N=10) diagnosed with MDS-AML (N=16) or de novo AML (N=6) at the time of VTX administration. Median age was 75 years. Average cytogenetic risk was 1.9 according to IPSS-R. Results: Median total dose of VTX was 1500 mg during standard azacitidine 5-2-2 regimen (75 mg/sqm, 28 day period) or standard LD-AraC regimen (10 mg or 20 mg, 28 day period). The average dose of VTX was 53 mg/day which is lower compared to therapeutic dose used in treatment of other hematologic malignancies due to risk of life-threatening cytopenia. In the group of de novo AML patients we observed ORR of 67% (CR=33%, PR=17%, HI=17%) with median OS on therapy of 6.5 months. In the group of MDS/AML patients we observed ORR of 57% (CR=29%, PR=21%, hematologic improvement (HI)=7%) with median OS on therapy of 5.4 months. We also included 13 patients (59%) after AZA failure as 1 st line of therapy and addition of VTX led to transient remission. Summary/Conclusion: Venetoclax in combination with azacitidine or LD-AraC provides an effective treatment for patients with de novo AML, MDS-AML or MDS patients after azacitidine failure. Total dose of venetoclax is significantly lower due to cytopenia. Reduction of azacitidine dose during first two cycles was associated with worse overall survival (p=0.0191). Mutation of TP53 was associated with worse overall survival (p=0.0184). Achieving of HI-P during first two cycles was associated with better overall survival (p=0.0341). Failure of combination therapy remains unclear and will be studied further.
P933: DARATUMUMAB (D) IN COMBINATION WITH VD OR D-RD IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS OF CASTOR AND POLLUX STUDIES IN PATIENTS WITH EARLY OR LATE RELAPSE AFTER INITIAL THERAPY
Authors: A. Spencer, P. Moreau, M.-V. Mateos, H. Goldschmidt, K. Suzuki, M.-D. Levin, P. Sonneveld, S.-S. Yoon, S. Z. Usmani, K. Weisel, D. Reece, T. Ahmadi, H. Pei, W. Garvin Mayo, X. Gai, J. Carey, R. Carson, M. A. Dimopoulos
Journal: HemaSphere (2022)

Background: High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities (ie, t[4;14], t[14;16], and/or del17p); however, patients who relapse early (12-18 months) after initial therapy are considered a functional high-risk group that is also associated with poor prognosis. Daratumumab (DARA), a human IgGk monoclonal antibody targeting CD38, is approved in combination with standard-of-care regimens for MM. In the phase 3 CASTOR and POLLUX studies, DARA in combination with bortezomib plus dexamethasone (D-Vd) and lenalidomide plus dexamethasone (D-Rd) significantly improved progression-free survival (PFS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (≥CR) and minimal residual disease (MRD)–negativity vs Vd or Rd alone in patients with RRMM. Aims: In this post-hoc analyses of CASTOR and POLLUX we evaluated D-Vd vs Vd and D-Rd vs Rd in patient subgroups with 1 prior line of therapy based on timing of relapse (early or late) after initiation of the first line of therapy. Methods: In CASTOR and POLLUX, patients with RRMM and ≥1 prior line of therapy were randomized to D-Vd/Vd or D-Rd/Rd, respectively. The primary endpoint was PFS. In this analysis, the early relapse subgroup included patients with 1 prior line of therapy who relapsed <18 months after initiating their first line of therapy; patients with 1 prior line of therapy who relapsed ≥18 months after initiating their first line of therapy were included in the late relapse subgroup. Results: 49 and 186 patients from CASTOR and 99 and 196 patients from POLLUX were included in the early relapse and late relapse subgroups, respectively. Median follow-up was 72.6 months (CASTOR) and 79.7 months (POLLUX). PFS consistently favored the DARA-containing regimens across subgroups (Table). In CASTOR, ≥CR rates were higher with D-Vd vs Vd in the early relapse (21% vs 17%; P = 0.7360) and late relapse (51% vs 14%; P <0.0001) subgroups. In POLLUX, ≥CR rates were higher with D-Rd vs Rd in the early relapse (53% vs 12%; P <0.0001) and late relapse (62% vs 38%; P = 0.0012) subgroups. MRD-negativity rates (10–5) were higher with D-Vd/D-Rd vs Vd/Rd regardless of relapse timing (CASTOR: early, 13% vs 0%; P = 0.1476; late, 23% vs 3%; P <0.0001; POLLUX: early, 30% vs 4%; P = 0.0006; late, 34% vs 14%; P = 0.0009). Image:Summary/Conclusion: These post hoc analyses of CASTOR and POLLUX showed PFS and depth of response benefits of DARA-containing regimens in patients with 1 prior line of therapy, regardless of relapse timing (early or late). Our results support the use of D-Vd and D-Rd in RRMM, including in patients who are considered functional high risk.
PB1888: EFFICACY OF FIRST-LINE TREATMENT FOR CHRONIC LYMPHOCYTIC LEUKEMIA: A BAYESIANNETWORK META-ANALYSIS.
Authors: A. Chanan-Khan, K. Yang, T. Liu, A. Cohen, K. Fahrbach, Y. Wang, B. Tang
Journal: HemaSphere (2022)

Background: Zanubrutinib is an oral, highly selective, next-generation Bruton tyrosine kinase inhibitor. Efficacy of zanubrutinib was compared with bendamustine + rituximab (BR) in adult patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) in the phase 3 SEQUOIA trial (NCT03336333). However, efficacy of zanubrutinib compared with other frontline CLL treatments remains unknown. Aims: The goal of this network meta-analysis of randomized controlled trials (RCTs) was to estimate the relative efficacy of zanubrutinib compared with standard frontline treatments for CLL. Methods: A total of 4 relevant RCTs were identified by a targeted literature review conducted throughout January 2022, CLL11 (NCT01010061), ALLIANCE (NCT01886872), MABLE (NCT01056510), and SEQUOIA. A feasibility assessment was performed to ensure that RCTs included within each population strata did not differ with respect to effect modifiers including presence of mutation, age, del11, and del17 status. A network was constructed for the composed 4 RCTs to compare the efficacy of zanubrutinib with bendamustine + rituximab, chlorambucil + obinutuzumab, chlorambucil + rituximab, and ibrutinib in patients with previously untreated CLL. Bayesian NMA models were conducted to simultaneously synthesize hazard ratio (HR) and 95% credible intervals (CI) for investigator-assessed progression-free survival (PFS). A constant hazard ratio was assumed in the NMA analysis. Statistical analyses were performed using codes suggested by the National Institute for Health and Care Excellence. Results: The efficacy results of the NMA indicated a statistically significant improvement in PFS for zanubrutinib over bendamustine + rituximab (HR = 0.42; [95% CI = 0.27, 0.65]), chlorambucil + obinutuzumab (0.45 [0.23, 0.86]), and chlorambucil + rituximab (0.22 [0.12, 0.41]). Zanubrutinib achieved comparable PFS to ibrutinib (1.07 [0.59, 1.94]). Image:Summary/Conclusion: This is the first NMA to compare the efficacy of zanubrutinib with all commonly utilized first-line treatment for TN CLL. Results from this indirect treatment comparison suggested that the PFS for zanubrutinib may be statistically significantly better than immunochemotherapy. Findings from this study require validation with further large scale RCTs with longer follow up time.
P1625: STATE OF CERTIFICATION IN TRANSFUSION SERVICES IN ANDALUSIA. LOW RATE OF CERTIFICATION IN COMMUNITY HOSPITALS
Authors: J. R. Garcia Fernandez
Journal: HemaSphere (2022)

Background: A quality management system certified bya an externel entity allows the development of a safe and efficient transfusion activity, while contributing to the involvement of all hospital staff to improving a continous quality system. In Spain there are two entities accredited by ENAC for certification in transfusion: Transfusion Accreditation Commitee (CAT) and the Agency for Health Quality of Andalusia (ACSA), although the latter with a specific program limited to transfusion centers not available for hospital practice. Aims: Describe the situation related to quality management system in transfusion medicine in Andalusia (a región in the south of Spain) in 2021. Methods: On the basis of data published by the CAT and ACSA we exposed the number of certified centers in Andalusia compared with to national data. Results: .-Although almost half transfusion centers in Andalusia are certified by CAT, 100 % of them are validated by the ACSA specific program. 2.- 29 % of centers accredited in Spain are accredited in Andalusia. 3.-The percentage of accreditation is related to the type of centers: 100 % in cord blood banks and transfusion centers; 75 % in big hospitals and only 12 % in little community hospitals. 4.-The relationship with the referral hospital and transfusion center seems to be the most important predisposing factor to maintain a certification program. Related to the certification program in the form of mangement, it´s not fully adapted to “little” hospitals, because if it´s true that there is a hospital responsable for haemovigilance, hemotherapy isn´t an exclusive dedication for him. Summary/Conclusion: The implementation of a management system certified quality by an external entity is a clear need in all transfusion centers, although the percentage of certified centers is less tahn 40 %, represented a 29 % of the certified centers nationwide. 2. Certification of transfusion services by CAT is the only feasible option, but its adaptation to “little” community hospitals is so difficult which is evident in view of the low number of certified centers. 3.Continuous quality improvement represents an additional workload sometimes unacceptable, it would be required a limited version adapted to general hospitals with low rate of transfusion and no specific staff transfusion related.
P1380: DEGREE OF CELL PACKING OF CRYOPRESERVED AT -80ºC HEMATOPOIETIC STEM CELLS DOES NOT AFFECT THEIR VIABILITY AND HEMATOLOGIC RECOVERY OF TRANSPLANTED MYELOMA PATIENTS
Authors: I. Tonev, S. Simeonov, K. Milcheva, K. Venkov, P. Ganeva, G. Arnaudov, M. Mincheff
Journal: HemaSphere (2022)

Background: Dimethylsulfoxide (DMSO) is toxic to both cryopreserved cells and patients. We are using a method for freezing at - 80ºC with 5% final DMSO concentration. Aims: In an attempt to further decrease the amount of infused DMSO we tested viability of cells and hematologic recovery of patients following cryopreservation with different degree of cell packing. Methods: We compared two groups of myeloma patients with low and high cryopreserved cells concentration. Cell suspension in the first group of 88 patients contained average 175x106 cells/ml (maximum 250x106 cells/ml) and in the second group of 175 patients the cells were completely packed by total plasma removal (average 391x106 cells/ml and maximum 597 x106 cells/ml) before adding the cryoprotectants resulting in a 60% decrease of the volume to be frozen. Cells were non-programmed frozen and stored at -80ºC in a solution with final concentrations of 5% DMSO, 3.6% hydroxyethyl starch (HES 450 000 mw) and 3% of human serum albumin. Stem cell viability was evaluated by trypan blue exclusion test. Cell dose in the first patient group was 2,62x106/kg (0,8–6,6), while in the second group it was 2,67x106/kg (1,5-6,8). Results: There was no statistically significant difference between the two myeloma patient groups. Viability was 97,0% (85-99) and 96,5 % (70-99) respectively. The neutrophil recovery was on day 11 (9-19) for the first and on day 11 (9-18) for the second group. Platelets recovered after 12 days for the first and the second group. Summary/Conclusion: Dimethylsulfoxide is toxic and induces many side effects following transplant (cardiac, neurologic, respiratory, etc.), which are dose dependent. Reducing them could be achieved by lowering the final DMSO concentration (5%) and by decreasing the volume of the frozen suspension. Our approach does not affect the cellular viability or the hematologic recovery of the patients following transplantation.
PB1982: DEEPENING OF RESPONSE IN PATIENTS WITH MULTIPLE MYELOMA AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION: A MULTICENTRIC STUDY IN A LATINO POPULATION
Authors: C. Bourlon, A. Leal-Alanis, C. Vargas-Serafin, K. Teran-de-la-Sancha, L. Tarin-Arzaga, D. Gomez-Almaguer, P. Colunga-Pedraza, A. Gomez-de Leon, G. Ruiz-Arguelles, I. Murrieta-Alvarez, M. Alvarado-Ibarra, J. M. Perez-Zuñiga, L. F. Amador-Medina, C. Garcia-Castillo, G. Cardoso-Yah
Journal: HemaSphere (2022)

Background: Over the last decades Multiple myeloma (MM) outcomes have shown a continuous improvement as novel drugs and maintenance therapy have been incorporated. However, availability of these resources is still limited in low- and middle-income countries (LMIC), where autologous stem cell transplant (ASCT) continues to be the best strategy to achieve better response and survival. Aims: Our aim was to analyze the deepening of response after ASCT and its impact over survival outcomes in newly diagnosed MM (NDMM) patients. Methods: Multicenter retrospective study that included patients ≥ 18 years of age with NDMM who received upfront ASCT as consolidation between 2015 and 2020 at six transplant centers in Mexico. Response after ASCT was defined as any improvement of response according to IMWG criteria. Novel agents were considered: proteasome inhibitors, immunomodulatory drugs, other than thalidomide, and monoclonal antibodies. Results: A total of 126 patients were included. The median age at diagnosis was 53.1 years (range 38-68) and 55% were male. Most common isotype was IgG (60.3%) and extramedullary disease was present in 12.2%. Regarding risk, 72.7% were classified as ISS ≥2 and 18.7% of patients evaluated had high-risk cytogenetics (n=64). Induction therapy with novel agents was administered to 77 patients (61.2%). Pre-ASCT, 73.1% had a very good partial response (VGPR) or better. Conditioning regimen was melphalan-based in 96%, with 15.9% being oral melphalan. Five patients received a tandem ASCT (4.0%) and 86 (68.3%) maintenance therapy, being thalidomide-based in 54.6%. Response after ASCT was evaluated in 86.5% (n=109), with an improvement of response in 27.5%. Patients with ≥VGPR were 82.5%. The median overall survival (OS) of the cohort was 119 months (90.0 – 149.34) and progression-free survival (PFS) was 67.1 months (61.3 - 72.8). Deepening and maintenance of response after ASCT were associated with a better OS, 119.7 vs. 63.0 months (p=0.017) (Figure 1). Image:Summary/Conclusion: This is the first multicenter study of a Latino population that reports the impact of transplant on response deepening and survival of NDMM patients. ASCT improved responses in almost 30% of our patients, being this related to an increased OS. It is of utmost importance to increase access to novel drugs in low- and middle-income countries, albeit ASCT continues to be the standard of care in patients with NDMM and demonstrated to be the best consolidation strategy to improve response and survival in our population and therefore its use should be promoted and expanded in LMIC.
When I use a word . . . . Counterfactual medical history: Milton’s poetry
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

If Milton’s blindness had been successfully prevented or treated, would he still have produced the poetry that he did after 1652? The three sonnets that deal specifically with his blindness would not have appeared. Nor would some passages in <i>Paradise Lost</i> and <i>Samson Agonistes</i>. There is no reason to suppose that he would not have written <i>Paradise Lost</i>, since he had planned some such epic for many years. And although, because of its subject matter, he might not have been inspired to write <i>Samson Agonistes</i>, he might well have found an alternative subject of equal interest. However, on the restoration to the throne of Charles II in 1660 an act was passed, The Act of Free and General Pardon, Indemnity and Oblivion, in which the names were published of those who were not pardoned for their part in the English civil war, and who were therefore condemned to death. It is thought that one reason that Milton was pardoned was that his blindness had been punishment enough. Had he not been blind, political expediency might have deprived us of his last three great poems.
PB1885: THE ROLE OF PET CT IN HAIRY CELL LEUKEMIA
Authors: G. itchaki, K. gurevich, M. Gorenberg, T. Tadmor
Journal: HemaSphere (2022)

Background: Currently Hairy Cell Leukemia guidelines recommend the routine use of chest X-ray and abdominal ultrasound as imaging workup PET- CT / CT has become a key tool in assessing disease spread and treatment response of several types of cancer in general and B-cell malignancies in particular. In HCL, the use of PET-CT has been reported mainly in patients who presents with unusual clinical sites of involvement or manifestation, and are available in the literature only as case reports. Aims: To characterize the typical baseline assessment of pet uptake in HCL with particular attention to BM involvement and SUV uptake in classical HCL, Extramedullary sites of involvement and Predictive value in response to therapy. Methods: Clinical laboratory and demographic data were summarized for HCL patients who performed PET CT during follow up in 2 medical centers in Israel. 2 central reviewer experts evaluated all PET CT test using the Deauville criteria. Results: The study included 8 patients diagnosed and follow up in 2 medical centers in israel with classical HCL. All patients included performed at least one PET CT with a total of 20 test median age was 50 (range 34-84) and 7 were males (14%). All pateinets recived at least 1 line of therapy. Indication for PET CT included investigation for infection, vasculitis, second cancers or extramiddolary disease. We will presnet median SUV uptake during active disease in BM, Spleen, and bone. Uptake in unusual site will be descibe. Pet results following therapy and correltion with response assesment will be presented. Summary/Conclusion: This study is pioneer in learning the role of PET CT inHCL. findings suggest that PET/CT may helpfully in identify extramidollary sites and reponse to therapy. Prospective clinical trials including larger cohorts of patients are needed to conclusively define the role and prognostic impact of PET/CT in HCL patients.
PB1786: COMPARISON OF OPTICAL GENOME MAPPING WITH STANDARD OF CARE TESTING TO INVESTIGATE GENOMIC ABNORMALITIES IN LEUKAEMIAS: THE EXPERIENCE OF THE CENTRAL AND SOUTH GENOMIC LABORATORY HUB, UK
Authors: M. Muraru, A. Skowronska, S. Dyer, A. Beggs, J. Woodley, C. Poxon, J. Mason
Journal: HemaSphere (2022)

Background: Here we present the Central and South Genomic Laboratory Hub experience of verifying Optical Genome Mapping (OGM). OGM a has great potential to become the new gold standard for detecting structural and copy number variations (SVs and CNVs) identified by cytogenetic techniques for routine use in a diagnostic laboratory environment. A range of haematological referrals were analysed by OGM and results were compared with standard of care testing consisting of G-band metaphase analysis, Fluorescence in Situ Hybridisation (FISH) and SNP array analysis. The use of OGM in various research and diagnostic labs is being validated and implemented around the world. Aims: Our objective was to compare the workflows in terms of processing and analysis times and concordance of results. Methods: This next generation cytogenomic technique consists of isolating ultra-high molecular weight DNA, genome wide labelling and imaging of the molecules using the Bionano Saphyr system. This allows the acquisition of big amount of data in parallel followed by analysis using the Bionano Access software. Bionano Genomics Rare Variant Pipeline (RVP) was used for somatic variant detection. Results: We show the concordance between standard of care tests and OGM in the analysed cohort and also present details of additional aberrations detected by OGM, due to its superior resolution and sensitivity compared to G-band analysis. Summary/Conclusion: With improvements to capacity on the Saphyr instrument, and automation of key processes, we believe that OGM has the potential to replace G-band chromosome analysis currently used as a global screen in routine diagnostics for haematological malignancy.